The accurate diagnosis of
malaria starts with clinical suspicion, confirmed by reliable laboratory results. A hospital-based study, described here, was carried out in a
malaria mesoendemic area in eastern Sudan, where the inhabitants are semi-immune to
malaria, and the
fever threshold of
parasitemia is not above the detection level of microscopy. Thus, we hypothesized that patients with symptoms highly suggestive of
cerebral malaria (CM), but aparasitemic by microscopy, may have submicroscopic
parasitemia. Patients in our
malaria clinic were screened by microscopy, and 120 individuals were selected for the study, including febrile patients with and without microscopically detectable
parasitemia, and apparently healthy individuals. In the two former groups there were patients with severe
anemia and deep
coma. Polymerase chain reaction (PCR) for parasite detection and ELISA tests for measuring serum antibody levels were carried out on all blood samples. A majority of the febrile patients who were parasite negative by microscopy showed the presence of a Plasmodium falciparum
infection by PCR. The occurrence of P. falciparum
infection with
parasitemia below the detection level of microscopy was recognized more often in patients with CM symptoms than in those with severe malarial
anemia (SMA), and in older rather than younger patients. Patients clinically suspected (CS) of having CM ((CS)CM) mostly were infected with a single clone, and a large proportion of them acquired
antibodies (Abs) against merozoite
surface protein (MSP)
antigens (Ags). The therapeutic response to
quinine treatment was comparable between patients with (CS)CM and CM. In conclusion, uniquely in this setting, CM can be associated with sub-patent
parasitemia; thus, a diagnostic tool more sensitive than microscopy is needed.